CYNK-101 in Combination with Trastuzumab and Pembrolizumab in Patients with Locally Advanced Unresectable or Metastatic HER2-Positive Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma

NCT05207722 | Terminated Phase 1 FDA Drug

• 1 other identifier: CYNK-101-HER2-001
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 3

Brief Summary

This study will find the maximum tolerated dose (MTD) of CYNK-101 which contains Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded. CYNK-101 will be administered as first-line treatment, following induction therapy consisting of Pembrolizumab, Trastuzumab and a Fluoropyrimidine / Platinum based Chemotherapy regimen. Patients are required to undergo a biopsy for confirmation of HER2 positivity defined as either IHC 3+ or IHC 2+ with a positive fluorescent in-situ hybridization (FISH) or FISH + alone. The safety of this treatment will be evaluated, and researchers will want to learn if NK cells will help in treating patients with Locally Advanced Unresectable or Metastatic HER2-Positive Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma.

Conditions

Metastatic HER2 Positive Gastroesophageal Junction Cancer

Keywords

CYNK-101; Natural Killer Cells; Cell Therapy; Metastatic HER2-positive Gastric Cancer; Gastric Cancer; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicity (DLT)

  Phase I

  up to 28 days

• Maximum Tolerated Dose (MTD)

  Phase I

  up to 28 days

• Overall Response Rate (ORR) as determined by the RECIST 1.1 Investigator using RECIST 1.1.

  Phase IIa

  up to 12 months

Secondary Outcomes (8)

• Progression Free Survival (PFS)

  at 6 and 12 months

• Duration of Response (DoR)

  up to 12 months

• Overall Response Rate (ORR) as determined by the RECIST 1.1

  up to 12 months

• Incidence of Response conversion post CYNK-101 infusion

  up to 12 months

• Incidence of Treatment Emergent adverse events (TEAE)

  up to 12 months

Study Arms (2)

Phase I Dose Escalation

EXPERIMENTAL

Up to two dosing cohorts of CYNK-101 in combination with rhIL2 will be evaluated following an initial induction and lymphodepletion regimen.

Biological: CYNK-101; Drug: Pembrolizumab; Drug: Trastuzumab; Drug: Recombinant Human Interleukin-2; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna

Phase IIa Expansion

EXPERIMENTAL

Once the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) is determined in Phase I, the Phase IIa portion of the study will commence.

Biological: CYNK-101; Drug: Pembrolizumab; Drug: Trastuzumab; Drug: Recombinant Human Interleukin-2; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna

Interventions

CYNK-101 BIOLOGICAL

CYNK-101 is a human placental hematopoietic stem/progenitor cell derived NK cell product, that is genetically modified to express a variant of CD16, Fc gamma receptor III (FcγRIII).

Phase I Dose Escalation; Phase IIa Expansion

Pembrolizumab DRUG

200 mg on Day 1 of each 3-week cycle as an IV infusion.

Also known as: Keytruda®

Phase I Dose Escalation; Phase IIa Expansion

Trastuzumab DRUG

8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.

Also known as: Herceptin®

Phase I Dose Escalation; Phase IIa Expansion

Recombinant Human Interleukin-2 DRUG

6 million (M) international units (IU) of rhIL-2 administered subcutaneously (SC) on each CYNK-101 infusion day.

Also known as: proleukin

Phase I Dose Escalation; Phase IIa Expansion

Cyclophosphamide DRUG

Cyclophosphamide: 900 mg/m2 administered IV as part of a 3-day lymphodepletion regimen.

Also known as: cytoxan

Phase I Dose Escalation; Phase IIa Expansion

Fludarabine DRUG

Fludarabine: 30 mg/m2 administered IV as part of a 3-day lymphodepletion regimen.

Also known as: fludara

Phase I Dose Escalation; Phase IIa Expansion

Mesna DRUG

MESNA: shall be administered as part of a 3-day lymphodepletion regimen for the inhibition of hemorrhagic cystitis induced by cyclophosphamide. Route of administration, dosage, and frequency of Mesna should be based on institutional standards.

Phase I Dose Escalation; Phase IIa Expansion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be at least 18 years of age on the day of signing informed consent.
• Have cytologically or histologically confirmed diagnosis for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-Positive Gastric or Gastroesophageal junction (G/GEJ) adenocarcinoma.

You may not qualify if:

• Patients will be required to undergo a biopsy for confirmation of HER2 expression prior to study entry.
• HER2 overexpression is defined by immunohistochemistry (IHC) or in situ hybridization (ISH) for amplification of HER2 gene.
• Patients must have either IHC 3+ or IHC 2+ with a positive fluorescent in-situ hybridization (FISH) or FISH + alone, as assessed locally on primary or metastatic tumor.
• Due to differences in tumor histopathology, use of FDA-approved tests, specific for Gastric Cancers, will be required when assessing HER2 Expression \[HERCEPTIN package insert; 202120\].
• Have measurable disease as assessed by the investigator according to RECIST 1.1 \[Eisenhauer EA et al, 200913\].
• Have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
• Have a life expectancy of ≥ 6 months.
• Patients must agree to use a highly effective method of contraception from the start of the study until 1 year after the last dose of lymphodepletion or 4 months from last dose of pembrolizumab, or 6 months from last dose of trastuzumab; whichever comes later.
• Have adequate cardiac function, defined as left ventricular ejection fraction \> 45% as determined by MUGA scan or ECHO and QT interval calculated according to the Fridericia method (≤ 470 ms for men and ≤480 ms for women).
• Demonstrate adequate organ function by laboratory values as follows:
• Hematological:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L,
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
• Renal:

Sponsors & Collaborators

• Celularity Incorporated: lead

Study Sites (3)

Scripps Health

La Jolla, California, 92037, United States

Location

Georgetown

Washington D.C., District of Columbia, 20057, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

pembrolizumab; Trastuzumab; aldesleukin; Cyclophosphamide; fludarabine; fludarabine phosphate; Mesna

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

Study Officials

• Adrian Kilcoyne, MD

  Celularity Incorporated

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This Phase I/IIa study will utilize a 3+3 open label design, and will evaluate two escalating dosing Cohort levels of CYNK-101 in combination with rhIL2 following and initial induction and lymphodepletion regimen. Once the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) is determined in Phase I, the Phase IIa portion of the study will commence.

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: January 26, 2022
• Study Start: April 14, 2022
• Primary Completion: February 15, 2024
• Study Completion: February 15, 2024
• Last Updated: December 12, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)